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  1. 学部学科区分一覧
  2. 医学部・医学系研究科・医学部附属病院
  1. 資料タイプ一覧
  2. 学術雑誌論文

Restoration of mutant hERG stability by inhibition of HDAC6

https://repository.lib.tottori-u.ac.jp/records/7264
https://repository.lib.tottori-u.ac.jp/records/7264
b53c59ee-761d-4a07-9e2b-1940f152a56a
名前 / ファイル ライセンス アクション
jmcc115_158.pdf jmcc115_158.pdf (567.9 kB)
Item type 学術雑誌論文 / Journal Article(1)
公開日 2021-11-24
タイトル
言語 en
タイトル Restoration of mutant hERG stability by inhibition of HDAC6
言語
言語 eng
キーワード
主題 hERG
キーワード
主題 HDAC6
キーワード
主題 Acetylation
キーワード
主題 Ubiquitination
キーワード
主題 LQT2
キーワード
言語 en
主題 hERG
キーワード
言語 en
主題 HDAC6
キーワード
言語 en
主題 Acetylation
キーワード
言語 en
主題 Ubiquitination
キーワード
言語 en
主題 LQT2
資源タイプ
資源タイプ journal article
著者 李, 佩俐

× 李, 佩俐

WEKO 1879
e-Rad 40464292
研究者総覧鳥取大学 100000877

李, 佩俐

ja-Kana リ, ペイリ

en Li, Peili

Search repository
倉田, 康孝

× 倉田, 康孝

WEKO 26952

倉田, 康孝

ja-Kana クラタ, ヤスタカ

Search repository
Mahati, Endang

× Mahati, Endang

WEKO 26953

Mahati, Endang

ja-Kana マハティ, エンダン

Search repository
二宮, 治明

× 二宮, 治明

WEKO 2609
e-Rad 80212124
研究者総覧鳥取大学 100000212

二宮, 治明

ja-Kana ニノミヤ, ハルアキ

en Ninomiya, Haruaki

Search repository
檜垣, 克美

× 檜垣, 克美

WEKO 685
e-Rad 90294321
研究者総覧鳥取大学 100000740

檜垣, 克美

ja-Kana ヒガキ, カツミ

en Higaki, Katsumi

Search repository
森川, 久未

× 森川, 久未

WEKO 2265
e-Rad 90707217

森川, 久未

ja-Kana モリカワ, クミ

en Morikawa, Kumi

Search repository
白吉, 安昭

× 白吉, 安昭

WEKO 3385
e-Rad 90249946
研究者総覧鳥取大学 100000304

白吉, 安昭

ja-Kana シラヨシ, ヤスアキ

en Shirayoshi, Yasuaki

Search repository
久留, 一郎

× 久留, 一郎

WEKO 765
e-Rad 60211504
研究者総覧鳥取大学 100000307

久留, 一郎

ja-Kana ヒサトメ, イチロウ

en Hisatome, Ichiro

Search repository
Kurata, Yasutaka

× Kurata, Yasutaka

WEKO 26954

en Kurata, Yasutaka

ja-Kana クラタ, ヤスタカ

Search repository
Mahati, Endang

× Mahati, Endang

WEKO 26955

en Mahati, Endang

ja-Kana マハティ, エンダン

Search repository
Taufiq, Fikri

× Taufiq, Fikri

WEKO 26956

en Taufiq, Fikri

Search repository
Horie, Minoru

× Horie, Minoru

WEKO 26957

en Horie, Minoru

Search repository
著者所属(英)
en
Department of Genetic Medicine and Regenerative Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University
著者所属(英)
en
Department of Physiology II, Kanazawa Medical University
著者所属(英)
en
Department of Genetic Medicine and Regenerative Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University
著者所属(英)
en
Department of Biological Regulation, Tottori University
著者所属(英)
en
Research Center for Bioscience and Technology, Tottori University
著者所属(英)
en
Department of Genetic Medicine and Regenerative Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University
著者所属(英)
en
Department of Genetic Medicine and Regenerative Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University
著者所属(英)
en
Department of Genetic Medicine and Regenerative Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University
著者所属(英)
en
Department of Cardiovascular Medicine, Shiga University of Medical Science
著者所属(英)
en
Department of Genetic Medicine and Regenerative Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University
抄録
内容記述タイプ Other
内容記述 The human ether-a-go-go-related gene (hERG) encodes the α subunit of a rapidly activating delayed-rectifier potassium (IKr) channel. Mutations of the hERG cause long QT syndrome type 2 (LQT2). Acetylation of lysine residues occurs in a subset of non-histone proteins and this modification is controlled by both histone acetyltransferases and deacetylases (HDACs). The aim of this study was to clarify effects of HDAC(s) on wild-type (WT) and mutant hERG proteins. WThERG and two trafficking-defective mutants (G601S and R752W) were transiently expressed in HEK293 cells, which were treated with a pan-HDAC inhibitor Trichostatin A (TSA) or an isoform-selective HDAC6 inhibitor Tubastatin A (TBA). Both TSA and TBA increased protein levels of WThERG and induced expression of mature forms of the two mutants. Immunoprecipitation showed an interaction between HDAC6 and immature forms of hERG. Coexpression of HDAC6 decreased acetylation and, reciprocally, increased ubiquitination of hERG, resulting in its decreased expression. siRNA against HDAC6, as well as TBA, exerted opposite effects. Immunochemistry revealed that HDAC6 knockdown increased expression of the WThERG and two mutants both in the endoplasmic reticulum and on the cell surface. Electrophysiology showed that HDAC6 knockdown or TBA treatment increased the hERG channel current corresponding to the rapidly activating delayed-rectifier potassium current (IKr) in HEK293 cells stably expressing the WT or mutants. Three lysine residues (K116, K495 and K757) of hERG were predicted to be acetylated. Substitution of these lysine residues with arginine eliminated HDAC6 effects. In HL-1 mouse cardiomyocytes, TBA enhanced endogenous ERG expression, increased IKr, and shortened action potential duration. These results indicate that hERG is a substrate of HDAC6. HDAC6 inhibition induced acetylation of hERG which counteracted ubiquitination leading its stabilization. HDAC6 inhibition may be a novel therapeutic option for LQT2.
書誌情報 Journal of Molecular and Cellular Cardiology
en : Journal of Molecular and Cellular Cardiology

巻 115, p. 158-169, 発行日 2018-02-28
出版者
出版者 Elsevier
ISSN
収録物識別子タイプ ISSN
収録物識別子 00222828
DOI
関連タイプ isVersionOf
識別子タイプ DOI
関連識別子 10.1016/j.yjmcc.2018.01.009
権利
権利情報 © 2018 Elsevier Ltd. All rights reserved.
情報源
関連名称 Li, Peili. Kurata, Yasutaka. Endang, Mahati. et al. Restoration of mutant hERG stability by inhibition of HDAC6. Journal of Molecular and Cellular Cardiology. 115. 158-169. 2018.
関連サイト
識別子タイプ URI
関連識別子 https://www.sciencedirect.com/science/article/pii/S002228281830018X
関連名称 https://www.sciencedirect.com/science/article/pii/S002228281830018X
著者版フラグ
出版タイプ AM
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